This invention is directed to an antimicrobial composition, and in particular to an antimicrobial composition including a mixture of fatty acids of differing lengths and a lipophilic polar solvent.
The treatment and prevention of mastitis in dairy cows continues to be of primary importance to those engaged in the dairy farming industry. The combined costs of mastitis to the U.S. dairy farming industry have been estimated at between two and three billion dollars annually.
Mastitis is caused by infections of the mammary, or milk-producing, glands by a broad spectrum of pathogenic microorganisms such as Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, Mycoplasma bovis and Candida albicans. In particular, when the milk-producing glands and surrounding tissues in the udder become infected, the tissues become inflamed with cellular infiltrates and associated toxic substances.
The cellular infiltrates and associated toxins, along with the infecting organisms themselves, can cause a dramatic reduction in the quality of milk produced by the animal. The infiltrates, toxins, and organisms can also affect the quantity of milk produced by the animal, possibly even resulting in the stoppage of production.
Occasionally, the infection can spread systemically to other organ and tissue sites via the blood or lymphatic systems. The spreading infection can, in extreme cases, seriously debilitate or kill the infected animal.
Given the importance of the mastitis problem to dairy farmers, several methods have been proposed to combat this menace. One method frequently used to combat the problem has been to xe2x80x9ccullxe2x80x9d out or separate the infected animals from the herd, and then to treat the infected animals with antibiotics. Antibiotics can be administered either directly (via an injection) or indirectly (via feed).
The secondary problem of antibiotic residues in the treated animals and their milk products, however, has come under increased scrutiny from federal and state regulatory agencies, such as the United States Department of Agriculture and the Food and Drug Administration. Additionally, public outcry over the use of antibiotics and the presence of antibiotics residues in meat and milk products has severely limited the market for such products.
As an alternative to treatment with antibiotics after infection, products have been designed to prevent mastitis by killing the pathogenic organisms which might otherwise infect the teat and udder tissues before the organisms enter the tissues. One such proactive product is a topical antiseptic commonly known as a teat (or udder) dip, wash, spray, or wipe. This product is applied to the teat and udder area of the dairy cow or other milk-producing animal before and/or after milking as part of a process of general dairy hygiene. The product is intended to kill or reduce in number the mastitis-causing microorganisms on the surface of the teat before the microorganisms have had a chance to migrate or be propelled (during milking) into the teat canal, or to enter the teat via injuries or lesions.
Although the wide-spread use of topical antiseptics in the last 30 years has greatly decreased the incidence of mastitis, many of the products presently in use as teat dips, washes, sprays or wipes (broad-spectrum chemical germicides such as chlorinated compounds, iodophors or chlorhexidines) are known to irritate the animals"" skin. This is particularly significant because the cow is subjected to repeated applications of the product, two or three times a day, before and/or after milking, for a period of years. In some cases, these germicides have actually been found to be toxic to the animals and to the human dairy workers.
Additionally, there is growing concern among the federal and state regulatory agencies, such as the Food and Drug Administration, about the presence of germicide residues, such as iodine or chlorhexidine, in milk products.
Furthermore, chemical germicides such as chlorine, iodine and chlorhexidine compounds lack a high degree of stability. These chemical germicides can be become inactivated over time, or can become inactivated by substances (such as water or organic materials) which may contaminate or dilute the germicide after it has been applied to the teat.
The lack of stability is a particularly significant disadvantage considering that, in some applications, teat dips, washes, sprays, and wipes are intended to remain on the teat and udder for hours at a time so as to provide extended protection from pathogenic microbes between milkings. In fact, for compounds such as chlorine dioxide, the lack of stability over time becomes even more significant in that the time between the preparation of the product by the farmer and the application of the product to the animal may be at least two or three hours. The lack of stability over time also negatively impacts the ability of the dairy farmer to store, for example, compositions made of chlorine dioxide for use at a later date.
One suggested substitute for the chlorinated compounds, iodophors and chlorhexidines presently used as teat dips are the fatty acids and their derivatives. The antimicrobial or germicidal properties of short to medium-chain fatty acids (C6 to C14) and their derivatives (such as esters) have been widely known for some time. See U.S. Pat. No. 4,406,884 to Fawzi and U.S. Pat. No. 5,208,257 to Kabara; Viegas, et al., Inhibition of Yeast Growth by octanoic and Decanoic Acids Produced during Ethanolic Fermentation, Applied and Environmental Microbiology, January 1989; J. J. Kabara, Toxicological, Bactericidal and Fungicidal Properties of Fatty Acids and Some Derivatives, Journal of American Oil Chemists"" Society, November 1979; J. Fay and R. Farias, Inhibitory Action of a Non-Metabolizable Fatty Acid on the Growth of Escherichia coli: Role of Metabolism and Outer Membrane Integrity, Journal of Bacteriology, December 1977; and J. J. Kabara, Antimicrobial Lipids: Natural and Synthetic Fatty Acids and Monoglycerides, Lipids, March 1977. Fatty acids have been included in the class of lipophilic weak acids which are generally considered to be an important class of antimicrobial agents. See Thomas R. Corner, Synergism in the Inhibition of Bacillus subtilin by Combinations of Lipophilic Weak Acids and Fatty Alcohols, Journal of Antimicrobial Agents and Chemotherapy, pp. 1082-85 (June 1981).
While highly bactericidal, undiluted fatty acids are irritating to the skin, and may even be corrosive. Fortunately, it has been found that dilute concentrations of fatty acids have antimicrobial efficacy. Hence, a significant amount of work has been done to prepare antimicrobial compositions using a fatty acid diluted, for example, with water.
Preparing such a composition diluted with water is complicated because short to medium-chain fatty acids are, at best, only slightly soluble in water. One solution to the relative insolubility of fatty acids has been to add hydrotropes to compositions containing low concentrations (0.1 to 5.0% by weight) of a mixture of fatty acids (C6 to C12) to solubilize the fatty acids. In such a composition, the shorter-chained fatty acids (C6 to C9) may actually assist the action of the hydrotrope by helping to solubilize the longer species, and thereby improving the longer species"" antimicrobial efficacy. See U.S. Pat. No. 4,404,040 to Wang, et al.
To maintain the antimicrobial action of the fatty acids in solution with water, however, the pH of the composition must be sufficiently low (below 4.0) to allow the acids to remain in their active free acid form. A strong organic or inorganic acid must be added to lower the pH so that the fatty acid can remain in its active form.
Alternatively, while teaching a fatty acid composition diluted with water, U.S. Pat. No. 4,406,884 to Fawzi et al. teaches away from solubilizing the fatty acids in water. Instead, Fawzi teaches that the antimicrobial efficacy of the fatty acids may be enhanced by supersaturating the aqueous phase of an aqueous lotion or gel with low concentrations of a mixture of short and medium-chain fatty acids. According to Fawzi, the supersaturated aqueous phase combined with the lipophilicity of the fatty acids provides the increased antimicrobial action, without resort to either a hydrotrope or solubilizer to maintain the fatty acids in solution with the water.
Fatty acids have been found to be more soluble in vehicles other than water. In fact, while not specifically suggested as an antimicrobial, it has been disclosed that high concentrations (5% by weight or more) of a single length of fatty acid (C10, for example) in solution with ethanol or propylene glycol may have some efficacy in the treatment of skin diseases, such as erythroquamose and papulose. See German Laid-Open Application No. 2,912,438 to Eckert et al.
A novel antimicrobial composition is disclosed including from about 60 to 95% of a lipophilic polar solvent, such as propylene glycol, ethylene glycol, glycerol, or isopropanol, and from about 0.5 to 5% of a mixture of C8 to C14 fatty acids. Other constituents of the present invention may include water, an alcohol (such as ethanol or propanol) or a mixture thereof.
Also disclosed is a novel method of killing harmful microbes on the udder of a milk-producing animal using the above-mentioned composition.
Accordingly, it is an object of the present invention to provide an effective antimicrobial potent enough to kill a broad-spectrum of harmful microorganisms.
It is another object of the invention to provide an effective antimicrobial which is non-irritating upon application.
It is a further object of the invention to provide an effective antimicrobial that is non-toxic to animals and to humans working with the animals.
It is an additional object of the invention to provide an effective antimicrobial that does not pose a significant health-risk as a residual in the milk produced by the animals to which it is applied.
It is still another object of the invention to provide an effective antimicrobial that is stable over time and with variations in concentration/contaminants, and provides an enhanced residual effect when applied to a teat or udder.
The preferred embodiment of the present invention is a solution of 70% by weight of propylene glycol as the primary solvent and 1.0% by weight of a mixture of C8 and C10 aliphatic fatty acids as the solute. The fatty acid mixture preferably includes 55% by weight C8 fatty acids and 40% by weight C10 fatty acids, with the remaining 5% by weight of the fatty acid mixture being made up of other short to medium-chain fatty acids. The remaining 29% by weight of the composition includes water as a secondary solvent, with trace concentrations of compatible perfumes and dyes. Additionally, a preservative such as methyl paraben or propyl paraben may be added to increase the life of the composition. These constituents are combined to form a solution using methods known to one of ordinary skill in the art.
The present invention is not limited to the composition of the preferred embodiment, but may contain a variety of primary and secondary solvents and solutes in accordance with the teachings of this disclosure. The concentrations of solvents and solutes may also be varied while remaining within the scope of the present invention.
For example, the primary solvent may be selected from the group of lipophilic polar solvents including propylene glycol, ethylene glycol, glycerol, and isopropanol. The secondary solvent may include water, an alcohol (such as ethanol or propanol) or a mixture thereof.
Preferably, the mixture of fatty acids is a combination of C8 and C10 aliphatic fatty acids. However, mixtures of short to medium-chain aliphatic fatty acids, such as C8, C10, C12 and C14 aliphatic fatty acids, are encompassed by the present invention.
Additionally, the concentration of the primary solvent may vary from about 60 to 95% by weight of the composition. The concentration of the solute may also vary from about 0.5 to 5% of the composition, and the C8 and C10 fatty acids in the solute may also vary about the preferred concentrations of 55% and 40%, respectively.
Formulations of the preferred embodiments have demonstrated impressive antimicrobial efficacy against a broad spectrum of mastitis-causing microorganisms, both in vitro in the laboratory and in vivo during testing with dairy cows. The formulations of the preferred embodiments have been shown to have germicidal efficacy comparable to such popular chemical germicides as the iodophors, chlorhexidine-based compounds and chlorine-based compounds. Additionally, the mixture of fatty acids with a lipophilic polar solvent as disclosed has been shown to be superior in action to compositions wherein a lipophilic polar solvent and a single length fatty acid is used.